OBJECTIVE To analyze the influential factors of drug-induced cholestatic liver disease （DIC） related to tigecycline （TGC）， and establish a prediction model for the risk of this adverse reaction. METHODS Data of 707 hospitalized patients who received TGC treatment in our hospital from August 2022 to August 2024 were collected and randomly divided into training set （n＝566） and test set （n＝141） at a ratio of 8∶2. Prediction variables were screened using the least absolute shrinkage and selection operator regression analysis. Multivariate Logistic regression analysis was used to screen the independent risk factors for TGC-related DIC， and a nomogram prediction model was drawn based on the above factors. The prediction performance of the model was evaluated by the receiver operator characteristic curve （ROC curve） and its area under the curve （AUC）. The accuracy of the model was assessed by the Hosmer-Lemeshow goodness-of-fit test and calibration curves. The clinical net benefit of the prediction model were evaluated by decision curve analysis. RESULTS Among the 707 patients， 93 patients developed DIC， with an incidence rate of 13.15%. Gender， age， high-dose administration of TGC， intensive care unit （ICU） admission， duration of medication of TGC， and concurrent use of antifungal drug voriconazole were independent risk factors for the occurrence of TGC-related DIC （P＜0.05）. The AUC of the training set model was 0.745 （95%CI： 0.687-0.801）， with a sensitivity of 76.6% and a specificity of 60.3%. The AUC of ROC curve of the test set model was 0.762 （95%CI： 0.650-0.900）， with a sensitivity of 81.3% and a specificity of 72.0%. The Hosmer-Lemeshow goodness-of-fit test for the training set， the χ 2 value was 5.187 and P was 0.737； and for the test set， the χ 2 value was 9.980 and P was 0.266. The mean absolute error of the calibration curve for the training set was 0.012， and for the test set， it was 0.038. The risk threshold range for the training set was 4%-45%， and for the test set， it was 4%-28%. CONCLUSIONS Age， gender， high-dose administration of TGC， ICU admission， duration of medication of TGC， and concurrent use of antifungal drug voriconazole are independent risk factors for TGC-related DIC. The established TGC-related DIC risk prediction model has good prediction performance and accuracy.

Non-small cell lung cancer （NSCLC）， as the most common subtype of lung cancer， has a high incidence and mortality rate among global cancer cases. Although modern medicine has made remarkable progress in the treatment of NSCLC with advances in screening technologies and continuous optimization of therapeutic regimens， current treatments inevitably result in adverse outcomes such as high tumor recurrence rates， significant toxic side effects， and poor quality of life for patients. Traditional Chinese medicine （TCM） holds that the core pathogenesis of lung cancer lies in ''deficiency of healthy Qi and excess of pathogenic factors''. It originates from congenital insufficiency or acquired malnourishment， leading to an imbalance of Yin and Yang， deficiency of healthy Qi， and inability to eliminate pathogenic factors. The interactions among Qi stagnation， phlegm accumulation， blood stasis， and toxins give rise to disease. The root is deficiency， while the manifestation is excess. Therefore， the treatment of lung cancer in TCM is generally guided by the principle of "supporting the healthy Qi and eliminating the pathogens". A large number of clinical and pharmacological studies have shown that TCM and its active components can， through multiple targets and mechanisms， alleviate postoperative and chemoradiotherapy-related adverse reactions， inhibit tumor growth and recurrence， and improve the quality of life of patients with NSCLC. It is worth noting that although extensive studies have been conducted on the therapeutic patterns and pharmacological mechanisms of TCM and its active substances in NSCLC treatment， issues such as the diversity of medicinal materials， the complexity of chemical components， the scientific basis of herbal compatibility， and the flexibility of dosage indicate that there is still considerable room for further clinical and basic research. This review summarizes recent literature on the clinical syndromes， drug selection， medication patterns， and pharmacological mechanisms of TCM and its active components in the treatment of NSCLC， aiming to provide guidance for clinical medication in TCM therapy for NSCLC and to deepen the understanding and research of its therapeutic mechanisms.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Cochlear nerve deficiency（CND） is a rare inner ear malformation characterized by a hypoplastic or absent cochlear nerve, resulting in variable hearing loss or total deafness, depending on the quantity of nerve fibers present. About 18% of congenital hearing loss are associated with CND. It is a disease of uncertain cause. The outcome of auditory implant in CND patients varies widely. This article will discuss the related issues of CND.
Humans ; Cochlear Nerve/abnormalities* ; Cochlear Implants ; Child ; Cochlear Implantation/methods* ; Deafness ; Hearing Loss

The quality of traditional Chinese medicine (TCM) prescriptions (TCMPs) is critical to clinical efficacy; however, evaluating their consistency and identifying sources of variability remain challenging. This study proposes an integrated strategy to assess the quality of 100 widely sold TCMPs. A "one-for-all" chromatographic method was employed to analyze 645 sample batches. This large-scale data collection enabled statistical evaluations, such as hierarchical cluster analysis (HCA) and similarity heatmap, to identify quality inconsistencies. The introduction of a TCM-specific mass spectrometry (MS) database allowed for rapid, automated annotation of chemicals across 100 prescriptions and facilitated the tracing of raw material sources. Results indicate that 19% of prescriptions exhibited chemical inconsistencies, which are associated with high market value, low pricing, and substantial price disparities. The MS database allowed rapid annotation of 761 and 673 compounds in positive and negative modes, respectively, in 100 TCMPs, with 73 prescriptions reported for the first time. The tracing efforts succeeded in identifying >40% of the raw material sources for 51 prescriptions. P93 (Yinianjin (YNJ)) is a case in which the chromatographic profiles from three manufacturers displayed inconsistencies. Analysis using the database traced divergent peaks to Rhei Radix et R hizoma (RRER). Verification with self-prepared samples confirmed that manufacturers utilized three distinct botanical sources. This integrated strategy provides a scalable framework for quality control in TCMPs.

Aconiti Lateralis Radix Praeparata (Fuzi) represents a significant traditional Chinese medicine (TCM) that exhibits both notable pharmacological effects and toxicity. Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components, primarily diterpenoid alkaloids. To comprehensively analyze the chemical variations between different Fuzi products, ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was employed to systematically characterize Shengfuzi, Heishunpian and Baifupian. A total of 249 diterpenoid alkaloids present in Shengfuzi were identified, while only 111 and 61 in Heishunpian and Baifupian were detected respectively, indicating substantial differences among these products. An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers. Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples, 8 robust markers distinguishing these products were identified, including AC1-propanoic acid-3OH, HE-glucoside, HE-hydroxyvaleric acid-2OH, dihydrosphingosine, N-dodecoxycarbonylvaline and three unknown compounds. Additionally, the MS imaging (MSI) technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi, revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian. The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products. This research provides valuable insights into the material basis for future investigations of different Fuzi products.
Diterpenes/chemistry* ; Alkaloids/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Aconitum/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Metabolomics ; Mass Spectrometry/methods* ; Plant Roots/chemistry* ; Molecular Structure

Objective·To investigate the efficacy and safety of a dose-reduced,all-oral lenalidomide/melphalan/prednisone acetate(RMP)regimen in elderly and frail patients with newly diagnosed multiple myeloma(NDMM).Methods·Elderly and frail NDMM patients who visited the Department of Hematology of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,and the Third People's Hospital of Kunshan from April 2018 to March 2024 were retrospectively included.Clinical data and laboratory indicators were collected,and all patients were treated with the RMP regimen.SPSS 27.0 and R software were used for statistical analysis.Independent t-test was applied to normally distributed quantitative data,Mann-Whitney U test to non-normally distributed quantitative data,and x2 test and Fisher's exact probability method to qualitative data.Kaplan-Meier survival curves and Log-rank test were used for survival analysis.Results·Among the 22 elderly and frail NDMM patients treated with RMP,the median age was 76.3(68.4,95.0)years,and the median follow-up time was 25.5 months.The overall response rate(ORR)was 68.2%,and the rate of≥very good partial response(VGPR)was 36.4%.The median progression-free survival(PFS)was 20.53 months.The median PFS in the≤75-year-old group was 25.23(95%CI 12.95?37.52)months,while in the>75-year-old group it was 18.23(95%CI 14.86?21.61)months.There was no significant difference between the two groups.The median PFS in the≥partial response(PR)group was 20.67(95%CI 13.57?27.76)months,and in the

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.